Abstract:

A method for producing 2-hydroxy-4-(methylthio)butyric acid which
comprises the following steps (A), (B) and (C): Step (A): step of
reacting 1,2-epoxy-3-butene with water to obtain 3-butene-1,2-diol, Step
(B): step of reacting 3-butene-1,2-diol with methanethiol to obtain
4-(methylthio)butane-1,2-diol, Step (C): step of oxidizing
4-(methylthio)butane-1,2-diol to obtain 2-hydroxy-4-(methylthio)butyric
acid.

Claims:

1. A method for producing 2-hydroxy-4-(methylthio)butyric acid which
comprises the following steps (A), (B) and (C):Step (A): step of reacting
1,2-epoxy-3-butene with water to obtain 3-butene-1,2-diol,Step (B): step
of reacting 3-butene-1,2-diol with methanethiol to obtain
4-(methylthio)butane-1,2-diol,Step (C): step of oxidizing
4-(methylthio)butane-1,2-diol to obtain 2-hydroxy-4-(methylthio)butyric
acid.

2. The method according to claim 1, wherein the reaction is conducted in
the presence of an acid in the step (A).

3. The method according to claim 2, wherein the acid is a silicate
containing at least one element selected from a group 5 element and a
group 6 element of the long periodic table as a constituent.

4. The method according to claim 3, wherein the silicate containing at
least one element selected from a group 5 element and a group 6 element
of the long periodic table is vanadium, tungsten or molybdenum.

5. The method according to claim 2, wherein the acid is a phosphoric acid
compound.

6. The method according to claim 1, wherein 1,2-epoxy-3-butene is
1,2-epoxy-3-butene obtained by oxidizing butadiene in the step (A).

7. The method according to claim 1, wherein the reaction is conducted in
the presence of a catalyst in the step (B).

8. The method according to claim 7, wherein the catalyst is an azo
compound.

9. The method according to claim 8, wherein the azo compound is an
azonitrile compound, an azoester compound, an azoamidine compound or an
azoimidazoline compound.

10. The method according to claim 7, wherein the catalyst is a
nitrogen-containing aromatic compound and an aliphatic carboxylic acid
compound.

11. The method according to claim 1, wherein 4-(methylthio)butane-1,2-diol
is oxidized by bringing 4-(methylthio)butane-1,2-diol into contact with a
microbial cell having an ability to convert 4-(methylthio)butane-1,2-diol
into 2-hydroxy-4-(methylthio)butyric acid or a treated material thereof
in the step (C).

12. The method according to claim 11, wherein the microorganism is at
least one kind of microorganisms selected from genus Alcaligenes, genus
Bacillus, genus Pseudomonas, genus Rhodobacter and genus Rhodococcus.

Description:

[0002]2-Hydroxy-4-(methylthio)butyric acid is an analog of the essential
amino acid 1-methionine, and it is an important compound for using for
feed additive. As methods for production thereof, a method comprising
adding methanethiol to acrolein to obtain 3-methylthiopropionaldehyde,
reacting 3-methylthiopropionaldehyde obtained with hydrogen cyanide to
obtain 2-hydroxy-4-methylthiobutyronitrile, and then hydrolyzing
2-hydroxy-4-methylthiobutyronitrile obtained with sulfuric acid has been
known (e.g. U.S. Pat. No. 4,524,077).

DISCLOSURE OF THE INVENTION

[0003]The present invention provides a method for producing
2-hydroxy-4-(methylthio)butyric acid which comprises the following steps
(A), (B) and (C):

[0004]Step (A): step of reacting 1,2-epoxy-3-butene with water to obtain
3-butene-1,2-diol,

[0007]First, the step (A): step of reacting 1,2-epoxy-3-butene with water
to obtain 3-butene-1,2-diol will be illustrated.

[0008]1,2-Epoxy-3-butene can be produced, for example, according to known
methods such as a method comprising reacting an oxidizing agent such as
oxygen, an organic peroxide and hydrogen peroxide with butadiene. As a
preferable method, a method comprising reacting butadiene with oxygen in
the presence of silver-containing catalyst, for example, described in
U.S. Pat. No. 4,897,498.

[0009]The reaction of 1,2-epoxy-3-butene and water is preferably conducted
in the presence of an acid. Examples of the acid include sulfuric acid; a
phosphoric acid compound; a strong acidic ion-exchange resin; a silicate
containing at least one element selected from a group 5 element and a
group 6 element of the long periodic table as a constituent (hereinafter,
simply referred to as the metal-containing silicate); and the like. Among
them, the phosphoric acid compound and the metal-containing silicate are
preferable.

[0010]When sulfuric acid is used as the acid, the reaction may be
conducted according to the method described in U.S. Pat. No. 5,250,743.
When the strong acidic ion-exchange resin is used as the acid, the
reaction may be conducted according to the method described in WO
91/15469.

[0011]The cases of using the phosphoric acid compound and the
metal-containing silicate will be illustrated below.

[0012]First, the case of using the phosphoric acid compound as the acid
will be illustrated.

[0013]Examples of the phosphoric acid compound include phosphoric acid,
phosphorous acid, hypophosphorous acid, metaphosphoric acid and
polyphosphoric acid. Commercially available one is usually used. The
phosphoric acid compound may be used as an aqueous solution.

[0014]The amount of the phosphoric acid compound to be used is usually
0.001 mole or more relative to 1 mole of 1,2-epoxy-3-butene. There is no
specific upper limit and it is practically 1 mole or less relative to 1
mole of 1,2-epoxy-3-butene considering economical viewpoint.

[0015]The amount of water to be used is usually 1 mole or more relative to
1 mole of 1,2-epoxy-3-butene. There is no specific upper limit and large
excess amount thereof, for example, 500 moles relative to 1 mole of
1,2-epoxy-3-butene, may be used also to serve as the solvent.

[0016]The reaction of 1,2-epoxy-3-butene and water is usually conducted by
mixing 1,2-epoxy-3-butene, water and the phosphoric acid compound in the
absence of a solvent or with using water as the solvent. The mixing order
is not particularly limited. The reaction may be conducted in the
presence of an organic solvent. Examples of the organic solvent include
an ether solvent such as diethyl ether, methyl tert-butyl ether and
tetrahydrofuran; an ester solvent such as ethyl acetate; a tertiary
alcohol solvent such as tert-butanol; and a nitrile solvent such as
acetonitrile and propionitrile, and these solvents may be used alone or
in a form of a mixture. The amount of the organic solvent to be used is
not particularly limited, and it is practically 100 parts by weight or
less per 1 part by weight of 1,2-epoxy-3-butene considering volume
efficacy.

[0017]The reaction is usually conducted under ordinary pressure conditions
and may be conducted under reduced pressure conditions or pressurized
conditions. The reaction temperature is usually -20 to 100° C.,
preferably 0 to 100° C.

[0019]After completion of the reaction, for example, 3-butene-1,2-diol can
be also isolated by adding water and/or a water-insoluble organic solvent
to the reaction liquid, if necessary, conducting extraction to obtain an
organic layer containing 3-butene-1,2-diol, and concentrating the organic
layer as it is or after washing with water or an alkaline water, if
necessary. Examples of the water-insoluble organic solvent include a
halogenated hydrocarbon solvent such as dichloromethane, chloroform and
chlorobenzene; an ether solvent such as diethyl ether and methyl
tert-butyl ether; and an ester solvent such as ethyl acetate, and the
amount thereof to be used is not particularly limited. Examples of the
alkaline water include an ammonia water; an aqueous alkali metal hydrogen
carbonate solution such an aqueous sodium hydrogen carbonate solution and
an aqueous potassium hydrogen carbonate solution; an alkali metal
carbonate such an aqueous sodium carbonate solution and an aqueous
potassium carbonate solution; and an aqueous alkali metal hydroxide
solution such as an aqueous sodium hydroxide solution and an aqueous
potassium hydroxide solution, and the concentration and the amount
thereof are not particularly limited.

[0020]Next, the case of using the metal-containing silicate as the acid
will be illustrated.

[0021]In the present invention, the metal-containing silicate is not
particularly limited as far as it is a silicate containing the group 5
element of the long periodic table, the group 6 element of the long
periodic table or the both elements thereof as a constituent.

[0022]Examples of the group 5 element of the long periodic table include
vanadium, niobium, tantalum and the like. Examples of the group 6 element
of the long periodic table include tungsten, molybdenum, chromium and the
like. Preferred are vanadium, molybdenum and tungsten, and more preferred
are vanadium and molybdenum.

[0023]The metal-containing silicate can be produced, for example, by a
method comprising reacting a metal oxide containing at least one element
selected from the group 5 element and the group 6 element of the long
periodic table as a constituent with a silicon compound in the presence
of an organic template, followed by washing or calcining the reaction
product obtained as described in EP 1473275 A, Applied Catalysis A:
General 179, 11 (1999), J. Chem. Soc., Chem. Commun., 2231 (1995), and
the like. Among them, a metal-containing silicate produced by using a
metal oxide which is obtained by reacting at least one compound selected
from a group 5 metal of the long periodic table, a group 6 metal of the
long periodic table, a compound containing the group 5 element of the
long periodic table and a compound containing the group 6 element of the
long periodic table (hereinafter, simply referred to as the metal or
compound) with hydrogen peroxide is preferable as the above-mentioned
metal oxide. The method for producing the metal-containing silicate
produced by using the metal oxide which is obtained by reacting the metal
or compound with hydrogen peroxide will be illustrated below.

[0024]Examples of the group 5 metal of the long periodic table include
vanadium metal, niobium metal and tantalum metal. Examples of the group 6
metal of the long periodic table include tungsten metal, molybdenum metal
and chromium metal. Examples of the compound containing the group 5
element of the long periodic table as a constituent include a vanadium
compound such as vanadium oxide, ammonium vanadate, vanadium carbonyl
complex, vanadium sulfate and vanadium sulfate ethylene diamine complex;
a niobium compound such as niobium oxide, niobium chloride and niobium
carbonyl complex; and a tantalum compound such as tantalum oxide and
tantalum chloride. Examples of the compound containing the group 6
element of the long periodic table as a constituent include a tungsten
compound such as tungsten boride, tungsten carbide, tungsten oxide,
ammonium tungstate and tungsten carbonyl complex; a molybdenum compound
such as molybdenum boride, molybdenum oxide, molybdenum chloride,
molybdenum carbonyl complex; and a chromium compound such as chromium
oxide and chromium chloride.

[0025]Among the metals or compounds, tungsten metal, the tungsten
compound, molybdenum metal, the molybdenum compound, vanadium metal and
the vanadium compound are preferable, and molybdenum metal, the
molybdenum compound, vanadium metal and the vanadium compound are more
preferable.

[0026]The metals or compounds may be used alone, or two or more kind
thereof may be used. Among the metals or compounds, there are metals or
compounds having hydrates and the hydrates may be used or anhydrous one
may be used for the present invention.

[0027]The metal oxide is obtained by reacting the metal or compound with
hydrogen peroxide. As hydrogen peroxide, an aqueous solution is usually
used. A solution of hydrogen peroxide in an organic solvent may be used
and it is preferred to use the aqueous hydrogen peroxide solution from
the viewpoint of easier handling. The concentration of hydrogen peroxide
in the aqueous hydrogen peroxide solution or in the solution of hydrogen
peroxide in the organic solvent is not particularly limited, but in view
of volume efficacy and safety, the practical concentration is 1 to 60% by
weight. As the aqueous hydrogen peroxide solution, a commercially
available one is usually used as it is, or if necessary, it may be used
after adjusting the concentration by dilution or concentration. The
solution of hydrogen peroxide in the organic solvent can be prepared, for
example, by extracting the aqueous hydrogen peroxide solution with the
organic solvent, or distilling the solution in the presence of the
organic solvent.

[0028]The amount of hydrogen peroxide to be used is usually 3 moles or
more, preferably 5 moles or more relative to 1 mole of the metal or
compound, and the upper limit thereof is not particularly defined.

[0029]The reaction of the metal or compound with hydrogen peroxide is
usually carried out in an aqueous solution. The reaction may be carried
out in an organic solvent such as an ether solvent such as diethyl ether,
methyl tert-butyl ether and tetrahydrofuran, an ester solvent such as
ethyl acetate, an alcohol solvent such as methanol, ethanol and
tert-butanol, a nitrile solvent such as acetonitrile and propionitrile,
or in a mixture of the organic solvent and water.

[0030]The reaction of the metal or compound with hydrogen peroxide is
usually conducted by contacting both of them. In order to improve
efficacy of contact between the metal or compound, and hydrogen peroxide,
the reaction is preferably carried out with stirring so as to
sufficiently disperse the metal or compound in a solution for preparing
the metal oxide. The reaction temperature is usually -10 to 100°
C.

[0031]By reacting the metal or compound with hydrogen peroxide in water,
in the organic solvent, or in the mixed solvent of water and the organic
solvent, all or a part of the metal or compound is dissolved, whereby, a
homogeneous solution or slurry containing the metal oxide can be
obtained. The metal oxide may be isolated from the homogeneous solution
or slurry, for example, by concentration or filtration followed to
preparing a metal-containing silicate, and the homogeneous solution or
slurry may be used as it is for preparing the metal-containing silicate.

[0032]As the silicon compound, a tetraalkoxysilane such as
tetramethoxysilane, tetraethoxysilane and tetraisopropoxysilane is
usually used. The silicon compound is usually used in such an amount that
silicon atoms are 4 moles or more relative to 1 mole of the metal atom of
the above-mentioned metal oxide, and the upper limit thereof is not
particularly defined.

[0033]Examples of the organic template include an alkylamine, a quaternary
ammonium salt and a nonionic surfactant, and the alkylamine and the
quaternary ammonium salt are preferable.

[0034]Examples of the alkylamine include a primary amine wherein a
hydrogen atom of ammonia is substituted with an alkyl group having 8 to
20 carbon atoms such as octylamine, nonylamine, decylamine, undecylamine,
dodecylamine, tridecylamine, tetradecylamine and eicosylamine; a
secondary amine wherein one of hydrogen atoms of the amino group of the
above-mentioned primary amine is substituted with a lower alkyl group
having 1 to 6 carbon atoms such as a methyl group; and a tertiary amine
wherein a hydrogen atoms of the amino group of the above-mentioned
secondary amine is substituted with a lower alkyl group having 1 to 6
carbon atoms, and the primary amine is preferable.

[0035]As the quaternary ammonium salt, those consisting of a quaternary
ammonium ion wherein four hydrogen atoms of the ammonium ion
(NH4.sup.+) are substituted with same or different four alkyl groups
having 1 to 18 carbon atoms and an anion such as a hydroxide ion, a
chloride ion and a bromide ion are exemplified. Specific examples thereof
include a quaternary ammonium hydroxide salt such as tetraethylammonium
hydroxide, tetrapropylammonium hydroxide, tetrabutylammonium hydroxide
and trimethyloctylammonium hydroxide; a quaternary ammonium chloride salt
such as tetraethylammonium chloride, tetrapropylammonium chloride,
tetrabutylammonium chloride and trimethyloctylammonium chloride; and a
quaternary ammonium bromide salt such as tetraethylammonium bromide,
tetrapropylammonium bromide, tetrabutylammonium bromide and
trimethyloctylammonium bromide, and the quaternary ammonium hydroxide is
preferable.

[0036]Examples of the nonionic surfactant include polyethylene glycol.

[0037]The organic template may be used as it is and by mixing with water
or a hydrophilic solvent described below. The amount of the organic
template to be used is usually 0.03 to 1 mole relative to 1 mole of the
silicon compound.

[0038]The reaction of the above-mentioned metal oxide with the silicon
compound in the presence of the organic template is usually conducted by
mixing three components in the presence of a solvent. Examples of the
solvent include water, the hydrophilic solvent and a mixture thereof, and
water and mixed solvent of water and the hydrophilic solvent are
preferable. Examples of the hydrophilic solvent include a hydrophilic
alcohol solvent such as methanol, ethanol and isopropanol; a hydrophilic
nitrile solvent such as acetnitrile; and a hydrophilic ether solvent such
as dioxane, and the hydrophilic alcohol solvent is preferable, and
methanol and ethanol are more preferable. The amount of the solvent to be
used is usually 1 to 1000 parts by weight relative to 1 part by weight of
the organic template.

[0039]The reaction temperature is usually 0 to 200° C.

[0040]After completion of the reaction, for example, the metal-containing
silicate can be produced by separating the reaction product by filtration
from the reaction liquid followed by washing or calcining the separated
reaction product. In case of washing the separated reaction product,
examples of the washing solvent include an alcohol solvent such as
methanol and ethanol, and water. The amount thereof to be used is not
particularly limited. In the case of calcining the separated reaction
product, the calcination temperature is usually 300 to 700° C.,
preferably 500 to 600° C., and the calcination time is usually 0.5
to 20 hours. The separated reaction product may be calcinated after
washing.

[0041]The metal-containing silicate thus obtained usually has pores of
which the average micropore diameter is 4 to 100 Å (calculated by BHJ
method based on the result measured by the nitrogen adsorption method)
and the specific surface area thereof is usually 100 m2/g or more
(calculated by BET multipoint method (p/p0=0.1) based on the result
measured by the nitrogen adsorption method).

[0042]Next, the reaction of 1,2-epoxy-3-butene and water using the
metal-containing silicate will be illustrated.

[0043]The amount of the metal-containing silicate to be used is usually
0.001 part by weight or more relative to 1 part by weight of
1,2-epoxy-3-butene. There is no specific upper limit and it is
practically 5 parts by weight or less per 1 part by weight of
1,2-epoxy-3-butene considering economical viewpoint.

[0044]The amount of water to be used is usually 1 mole or more relative to
1 mole of 1,2-epoxy-3-butene. There is no specific upper limit and large
excess amount thereof, for example, 500 moles relative to 1 mole of
1,2-epoxy-3-butene, may be used also to serve as the solvent.

[0045]The reaction of 1,2-epoxy-3-butene and water is usually conducted by
mixing 1,2-epoxy-3-butene, water and the metal-containing silicate in the
absence of a solvent or with using water as the solvent, and the mixing
order is not particularly limited. The reaction may be carried out in the
presence of an organic solvent. Examples of the organic solvent include
an ether solvent such as diethyl ether, methyl tert-butyl ether and
tetrahydrofuran; an ester solvent such as ethyl acetate; a tertiary
alcohol solvent such as tert-butanol; and a nitrile solvent such as
acetonitrile and propionitrile. These solvents may be used alone or in a
form of a mixture. The amount of the organic solvent to be used is not
particularly limited, and it is practically 100 parts by weight or less
per 1 part by weight of 1,2-epoxy-3-butene considering volume efficacy.

[0046]The reaction is usually conducted under ordinary pressure conditions
and may be conducted under reduced pressure conditions or pressurized
conditions. The reaction temperature is usually -20 to 100° C.,
preferably 0 to 100° C.

[0048]After completion of the reaction, 3-butene-1,2-diol can be isolated
by concentrating a filtrate obtained by filtering off the
metal-containing silicate. 3-Butene-1,2-diol can be also isolated by, if
necessary, adding water and/or a water-insoluble organic solvent to the
above-mentioned filtrate, followed by extracting to obtain an organic
layer containing 3-butene-1,2-diol and concentrating the organic layer as
it is or after washing with water or an alkaline water, if necessary.

[0049]3-Butene-1,2-diol thus obtained can be used in the step (B)
described below as it is or after further purifying by conventional
purification means such as distillation and column chromatography.
3-Butene-1,2-diol may be used as a solution such as the above-mentioned
filtrate or organic layer without isolating 3-butene-1,2-diol.

[0050]Next, the step (B): step of reacting 3-butene-1,2-diol with
methanethiol to obtain 4-(methylthio)butane-1,2-diol will be illustrated.

[0051]As methanethiol, commercially available one may be used and one
produced from methanol and hydrogen sulfide. Gaseous methanethiol may be
used and liquid methanethiol may be used. Liquid methanethiol can be
prepared, for example, by a method comprising bringing gaseous
methanethiol into a container cooled below the boiling point thereof
(6° C.) to condense it.

[0052]The amount of methanethiol to be used is usually 1 mole or more
relative to 1 mole of 3-butene-1,2-diol. There is no upper limit
particularly and considering economical viewpoint, the amount thereof is
practically 10 moles or less relative to 1 mole of 3-butene-1,2-diol.

[0053]The reaction of 3-butene-1,2-diol and methanethiol is usually
carried out in the absence of a solvent, and the reaction may be carried
out in the presence of a solvent. The solvent is not particularly limited
in so far as it does not prevent the reaction. Examples thereof include
water; a hydrocarbon solvent such as hexane, heptane and toluene; a
halogenated hydrocarbon solvent such as chlorobenzene and chloroform; an
ether solvent such as diethyl ether, methyl tert-butyl ether and
tetrahydrofuran; an ester solvent such as ethyl acetate; a tertiary
alcohol solvent such as tert-butanol; and a nitrile solvent such as
acetonitrile and propionitrile. They may be used alone or in a form of a
mixture. The amount thereof to be used is not particularly limited, and
it is practically 100 parts by weight or less per 1 part by weight of
3-butene-1,2-diol considering volume efficacy.

[0054]The reaction is usually conducted under ordinary pressure conditions
or pressurized conditions, and may be conducted under reduced pressure
conditions.

[0055]The reaction of 3-butene-1,2-diol and methanethiol is preferably
conducted in the presence of a catalyst. Examples of the catalyst include
known catalysts such as an organic peroxide and a boron compound. In the
case of using the known catalyst such as the organic peroxide and the
boron compound, the reaction can be conducted according to methods
described in J. of Agricultural and Food Chemistry, 23, 1137 (1975) and
EP 1260500 A.

[0056]As the catalyst of the present step (B), an azo compound can be also
used. In the present step (B), the azo compound is preferably used as the
catalyst. Herein, the azo compound means a compound which has an azo bond
(--N═N--) within the molecule and of which decomposition temperature
is below 250° C. Examples thereof include an azonitrile compound
such as 2,2'-azobisisobutyronitrile,
2,2'-azobis(2,4-dimethylvaleronitrile),
2,2'-azobis(2-methylbutyronitrile),
1,1'-azobis(cyclohexane-1-carbonitrile), 4,4'-azobis-4-cyanopentanoic
acid, 2-phenylazo-2,4-dimethyl-4-methoxyvaleronitrile and
2-cyano-2-propylazoformamide; an azoester compound such as
azobisisobutanol diacetate, methyl azobisisobutyrate and ethyl
azobisisobutyrate; an azoamidine compound such as
2,2'-azobis(2-amidinopropane) dihydrochloride; an azoimidazoline compound
such as 2,2'-azobis[2-(2-imidazolin-2-yl)propane]; an azoamide compound
such as 1,1'-azobisformamide, 1,1'-azobis(N-methylformamide) and
1,1'-azobis(N,N-dimethylformamide); and an azoalkyl compound such as
azo-tert-butane. Preferred are the azonitrile compound, the azoester
compound, the azoamidine compound and the azoimidazoline compound. The
commercially available azo compound is usually used.

[0057]The amount of the azo compound to be used is usually 0.001 mole or
more relative to 1 mole of 3-butene-1,2-diol. There is no specific upper
limit and it is practically 0.2 mole or less relative to 1 mole of
3-butene-1,2-diol considering economical viewpoint.

[0058]The reaction temperature in the case of using the azo compound as
the catalyst differs depending on kinds of the azo compound to be used
and the amount thereof, and when the reaction temperature is too low, the
reaction hardly proceeds and, when the reaction temperature is too high,
side reaction such as polymerization of 3-butene-1,2-diol and the product
may proceed. Therefore, the reaction is usually conducted in the range of
-10 to 100° C., preferably of 0 to 50° C.

[0059]As the catalyst of the present step (B), a nitrogen-containing
aromatic compound and an aliphatic carboxylic acid compound can be also
used. In the present step (B), the nitrogen-containing aromatic compound
and the aliphatic carboxylic acid compound are also preferably used as
the catalyst.

[0060]The nitrogen-containing aromatic compound may be a monocyclic or
condensed ring C3-C20 heteroaromatic compound in which at least one of
atoms constituting the aromatic ring is a nitrogen atom. One or two or
more of hydrogen atoms constituting the above-mentioned aromatic ring may
be replaced with a substituent or substituents. Examples of the
substituent include a halogen atom such as a fluorine, chlorine and
bromine atom; a C1-C4 alkyl group such as a methyl, ethyl, n-propyl,
isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl group; a C1-C4
alkoxy group such as a methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy,
isbbutoxy, sec-butoxy and tert-butoxy group; a C2-C5 alkoxycarbonyl group
such as a methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl,
isopropoxycarbonyl, n-butoxycarbonyl, and tert-butoxycarbonyl group; an
amino group; and a carbamoyl group.

[0062]The amount of the nitrogen-containing aromatic compound to be used
is usually 0.001 mole or more relative to 1 mole of 3-butene-1,2-diol.
There is no specific upper limit and it is practically 1 mole or less
relative to 1 mole of 3-butene-1,2-diol considering economical viewpoint.

[0066]The reaction of 3-butene-1,2-diol and methanethiol is usually
conducted by mixing the catalyst, 3-butene-1,2-diol and methanethiol, and
the mixing order is not particularly limited. When the reaction is
conducted under ordinary pressure conditions, the reaction is usually
conducted by a method comprising adjusting a mixture of the catalyst and
3-butene-1,2-diol at a given temperature and blowing gaseous methanethiol
into them. When the reaction is conducted under pressurized conditions,
the reaction is conducted, for example, by a method comprising adding the
catalyst and 3-butene-1,2-diol into a container capable of sealing such
as autoclave, sealing the container and pressing gaseous methanethiol
into it at a given temperature, and a method comprising adding the
catalyst, 3-butene-1,2-diol and liquid methanethiol into the
above-mentioned sealing container, sealing the container and adjusting at
a given temperature. In the case of mixing 3-butene-1,2-diol,
methanethiol and the catalyst followed by adjusting at a given
temperature to effect reaction or in the case of mixing 3-butene-1,2-diol
with methanethiol followed by adding the catalyst thereto to effect
reaction, the amount of methanethiol in the mixture containing
3-butene-1,2-diol and methanethiol is preferably 4 moles or less relative
to 1 mole of 3-butene-1,2-diol in order to start the reaction smoothly.

[0068]When an lipophilic catalyst is used as the catalyst, after
completion of the reaction, for example, 4-(methylthio)butane-1,2-diol
can be isolated by removing methanethiol remained from the reaction
mixture, and then, if necessary, adding water or an apolar solvent
thereto, followed by extracting and concentrating the obtained aqueous
layer containing 4-(methylthio)butane-1,2-diol. When a hypophilic
catalyst is used as the catalyst, for example,
4-(methylthio)butane-1,2-diol can be isolated by removing methanethiol
remained from the reaction mixture, and then, if necessary, adding water
or a water-insoluble organic solvent thereto, followed by extracting and
concentrating the obtained organic layer containing
4-(methylthio)butane-1,2-diol. Examples of the method for removing
methanethiol remained from the reaction mixture include a method
comprising concentrating the reaction mixture and a method comprising
blowing an inert gas such as nitrogen gas into the reaction mixture.
Examples of the apolar solvent include a hydrocarbon solvent such as
hexane, heptane, toluene and xylene, and the amount thereof to be used is
not particularly limited. Examples of the water-insoluble organic solvent
include an ester solvent such as ethyl acetate and an ether solvent such
as methyl tert-butyl ether besides the above-mentioned hydrocarbon
solvent, and the amount thereof to be used is not particularly limited.

[0069]When the nitrogen-containing aromatic compound and the aliphatic
carboxylic acid compound are used as the catalyst, after completion of
the reaction, for example, 4-(methylthio)butane-1,2-diol can be isolated
by removing methanethiol remained from the reaction mixture, and then, if
necessary, adding water-insoluble organic solvent thereto, followed by
extracting, washing the obtained organic layer containing
4-(methylthio)butane-1,2-diol with water, an acidic water and/or an
alkaline water and concentrating thereof.

[0070]4-(Methylthio)butane-1,2-diol obtained can be used in the step (C)
described below as it is or after further purifying by conventional
purification means such as distillation and column chromatography.
4-(Methylthio)butane-1,2-diol may be used as a solution such as the
above-mentioned organic layer without isolating
4-(methylthio)butane-1,2-diol.

[0071]Finally, the step (C): step of oxidizing
4-(methylthio)butane-1,2-diol to obtain 2-hydroxy-4-(methylthio)butyric
acid will be illustrated.

[0072]In the present invention, the oxidation of the primary alcohol
moiety within molecule of 4-(methylthio)butane-1,2-diol generally
proceeds in priority to the oxidation of the secondary alcohol moiety and
sulfide moiety.

[0073]Examples of the method for oxidizing 4-(methylthio)butane-1,2-diol
to obtain 2-hydroxy-4-(methylthio)butyric acid include a method
comprising conducting Swern oxidation of 4-(methylthio)butane-1,2-diol
followed by oxidizing with silver nitrate and a method comprising
bringing 4-(methylthio)butane-1,2-diol into contact with a microbial cell
having an ability to convert 4-(methylthio)butane-1,2-diol into
2-hydroxy-4-(methylthio)butyric acid or a treated material thereof.
Preferable example is the method comprising bringing
4-(methylthio)butane-1,2-diol into contact with a microbial cell having
an ability to convert 4-(methylthio)butane-1,2-diol into
2-hydroxy-4-(methylthio)butyric acid or a treated material thereof.

[0074]The method comprising conducting Swern oxidation of
4-(methylthio)butane-1,2-diol followed by oxidizing with silver nitrate
can be conducted, for example, according to the method described in
Tetrahedron, 48, 6043 (1992).

[0075]The method comprising bringing 4-(methylthio)butane-1,2-diol into
contact with a microbial cell having an ability to convert
4-(methylthio)butane-1,2-diol into 2-hydroxy-4-(methylthio)butyric acid
or a treated material thereof will be illustrated.

[0078]As the microorganisms, at least one kind of microorganisms selected
from genus Alcaligenes, genus Bacillus, genus Pseudomonas, genus
Rhodobacter and genus Rhodococcus is preferable, at least one kind of
microorganisms selected from genus Bacillus, genus Pseudomonas and genus
Rhodococcus is more preferable, at least one kind of microorganisms
selected from genus Pseudomonas and genus Rhodococcus is furthermore
preferable, and microorganism belonging to genus Rhodococcus is
especially preferable.

[0081]The culturing temperature and pH of the culturing liquid are not
particularly limited as far as in the range wherein a microorganism
grows, and the culturing temperature is usually about 15 to 40°
C., and the pH of the culturing liquid is usually about 4 to 8. The
culturing time can be accordingly selected depending on the culturing
conditions and it is usually about 1 to 10 days.

[0082]The microbial cell can be used as it is. Examples of the method of
using the fungus body of the microbial cell as it is include (1) method
comprising using the culturing liquid as it is and (2) method comprising
correcting the cell by centrifugal separation of the culturing liquid and
using the fungus body corrected (the wet cell after washing with buffer
liquid or water, if necessary).

[0083]The treated materials thereof can be used. Examples of the treated
materials include those obtained by treating the cell obtained by
culturing with an organic solvent (acetone, ethanol and the like), with
freeze-drying or with an alkali, those obtained by disrupting physically
or enzymatically, and crude enzyme separated and extracted from these
materials. Further, the treated materials of the cell also include those
obtained by subjecting the above-mentioned treatment followed by
conducting immobilizing treatment according to the known method.

[0084]4-(Methylthio)butane-1,2-diol is oxidized to obtain
2-hydroxy-4-(methylthio)butyric acid by bringing the microbial cell or
treated materials thereof into contact with
4-(methylthio)butane-1,2-diol.

[0085]The amount of the microbial cell or treated materials thereof to be
used is an amount that the concentration of the microbial cell or treated
materials thereof in the reaction liquid is usually 0.001 to 50% by
weight, and preferably 0.01 to 20% by weight.

[0086]The reaction of the microbial cell or treated materials thereof and
4-(methylthio)butane-1,2-diol is usually carried out in the presence of
water. As water, an aqueous buffering solution may be used and examples
of the buffering agent used for the aqueous buffering solution include an
alkali metal salt of phosphoric acid such as sodium phosphate and
potassium phosphate; and an alkali metal salt of acetic acid such as
sodium acetate and potassium acetate. The microbial cell or treated
materials thereof may be reacted with 4-(methylthio)butane-1,2-diol in
the presence of water and an organic solvent. The organic solvent may be
a hydrophobic organic solvent or a hydrophilic organic solvent. Examples
of the hydrophobic organic solvent include ester solvents such as ethyl
formate, ethyl acetate, propyl acetate, butyl acetate, ethyl propionate
and butyl propionate; hydrophobic alcohol solvents such as n-butyl
alcohol, n-amyl alcohol and n-octyl alcohol; aromatic hydrocarbon
solvents such as benzene, toluene and xylene; hydrophobic ether solvents
such as diethyl ether, diisopropyl ether and methyl tert-butyl ether;
halogenated hydrocarbon solvents such as chloroform and
1,2-dichloroethane; and a mixed solvent thereof. Examples of the
hydrophilic organic solvent include hydrophilic alcohol solvents such as
methanol and ethanol; hydrophilic ketone solvents such as acetone;
hydrophilic ether solvents such as dimethoxyethane, tetrahydrofuran and
dioxane; and a mixed solvent thereof.

[0087]The pH of reaction of the microbial cell or treated materials
thereof and 4-(methylthio)butane-1,2-diol is usually in the range of 3 to
10, and the reaction temperature is usually 0 to 60° C. The
reaction time is usually 0.5 hour to 10 days.

[0088]The concentration of 4-(methylthio)butane-1,2-diol in the reaction
liquid is usually 50% (w/v) or less.

[0089]The reaction of the microbial cell or treated materials thereof and
4-(methylthio)butane-1,2-diol is usually conducted by mixing the both.
The reaction may be conducted by adding 4-(methylthio)butane-1,2-diol
continuously or successively to the reaction system.

[0090]If necessary, sugars such as glucose, sucrose and fructose, or a
surfactant such as TritonX-100 and Tween60 may be added to the reaction
system.

[0091]The ending point of the reaction can be confirmed by monitoring the
amount of 4-(methylthio)butane-1,2-diol in the reaction liquid by liquid
chromatography or gas chromatography.

[0092]After the completion of the reaction,
2-hydroxy-4-(methylthio)butyric acid can be isolated by conducting
conventional aftertreatment of the reaction liquid such as extract
treatment and concentration treatment. 2-Hydroxy-4-(methylthio)butyric
acid obtained can be further purified by conventional purification means
such as column chromatography and distillation.

EXAMPLES

[0093]The present invention will be further illustrated by Examples in
detail below, but the present invention is not limited by these Examples.

[0094]Each of the specific surface area and the average micropore diameter
of the metal-containing silicate obtained were measured at 150° C.
under a degassed condition of 1.35×10-5 Kg/cm2
(equivalent of 0.013 kPa) by the nitrogen adsorption method using
Autosorb-6 manufactured by Quantachrome Instruments, and the specific
surface area and the average micropore diameter thereof were calculated
using BET multipoint method (p/p0=0.1) and BHJ method respectively.

Reference Example 1

[0095]To a 500 mL flask equipped with a stirrer, 5 g of a tungsten metal
powder and 25 g of ion-exchanged water were added, and an inner
temperature was adjusted to 40° C. 15 g of a 60% by weight aqueous
hydrogen peroxide solution was added dropwise thereto over 30 minutes,
and then the mixture was maintained at the same temperature for 1 hour to
obtain a solution containing tungsten oxide. To the solution containing
tungsten oxide, 75 g of ion-exchanged water and 80 g of ethanol were
added, and then 41.6 g of tetraethoxysilane was added dropwise thereto
over 10 minutes. Further, 20 g of 40% by weight aqueous
tetrabutylammonium hydroxide solution was added dropwise thereto at the
same temperature over 10 minutes. Then, the mixture was cooled to an
inner temperature of 25° C. and stirring was continued at the same
temperature, and solid was precipitated in about 30 minutes to form
slurry. After stirring and maintaining at the same temperature for 24
hours, solid was collected by filtration. Solid filtrated was washed
twice with 100 g of ion-exchanged water, and then dried at 130° C.
for 24 hours to obtain 38.0 g of the white solid. The white solid
obtained was calcined at 550° C. for 6 hours to obtain 16.5 g of
the white tungsten-containing silicate.

[0096]XRD spectrum: A broad peak having an apex at a d value of 3.77 Å
is observed. A peak assignable to tungsten oxide is not observed.

[0101]To a 500 mL flask equipped with a stirrer, 5 g of a tungsten metal
powder and 25 g of ion-exchanged water were added, and an inner
temperature was adjusted to 40° C. 15 g of a 60% by weight aqueous
hydrogen peroxide solution was added dropwise thereto over 30 minutes,
and then the mixture was maintained at the same temperature for 2 hours
to obtain a solution containing tungsten oxide. To the solution
containing tungsten oxide, 75 g of ion-exchanged water and 80 g of
ethanol were added, and then 41.6 g of tetraethoxysilane was added
thereto at an inner temperature of 40° C. over 10 minutes.
Further, 40 g of a 10% by weight tetrapropylammonium hydroxide solution
was added dropwise thereto at the same temperature over 10 minutes. Then,
the mixture was cooled to an inner temperature of 25° C. and
stirring was continued at the same temperature. Solid was precipitated in
about 30 minutes to form slurry. After stirring and maintaining at the
same temperature for 24 hours, solid was collected by filtration. Solid
filtrated was washed twice with 100 g of ion-exchanged water and dried at
130° C. for 24 hours to obtain 38.0 g of white solid. The white
solid obtained was calcined at 550° C. for 6 hours to obtain 17.3
g of a white tungsten-containing silicate.

[0102]XRD spectrum: A broad peak having an apex at a d value of 3.76 Å
is observed. A sharp peak assignable to tungsten oxide is slightly
observed.

[0107]To a 500 mL flask equipped with a stirrer, 2 g of a molybdenum metal
powder and 25 g of ion-exchanged water were added, and an inner
temperature was adjusted to 40° C. 15 g of a 60% by weight aqueous
hydrogen peroxide solution was added dropwise thereto over 1 hour, and
then the mixture was maintained at the same temperature for 1 hour to
obtain a solution containing molybdenum oxide. To the solution containing
molybdenum oxide, 75 g of ion-exchanged water and 80 g of ethanol were
added, and then 41.6 g of tetraethoxysilane was added thereto at an inner
temperature of 40° C. over 10 minutes. Further, 10 g of
dodecylamine was added dropwise thereto at the same temperature over 10
minutes. Solid was immediately precipitated to form slurry. The mixture
was cooled to an inner temperature of 25° C. and stirred and
maintained for 24 hours, and then solid was collected by filtration.
Solid filtrated was washed twice with 100 g of ion-exchanged water, dried
at 110° C. for 6 hours and calcined at 550° C. for 6 hours
to obtain 15.5 g of a white molybdenum-containing silicate.

[0108]XRD spectrum: A mixed spectrum of a broad peak having an apex at a d
value of 3.8 Å and a sharp peak assignable to molybdenum oxide is
observed.

[0113]It was confirmed that the white molybdenum-containing silicate
obtained had molybdenum oxide from these results.

Reference Example 4

[0114]To a 500 mL flask equipped with a stirrer, 2.5 g of a molybdenum
metal powder and 25 g of ion-exchanged water were added, and an inner
temperature was adjusted to 40° C. 15 g of a 60% by weight aqueous
hydrogen peroxide solution was added dropwise thereto over 1 hour, and
then the mixture was maintained at the same temperature for 1 hour to
obtain a solution containing molybdenum oxide. To the solution containing
molybdenum oxide, 75 g of ion-exchanged water and 80 g of ethanol were
added, and then 41.6 g of tetraethoxysilane was added thereto at an inner
temperature of 40° C. over 10 minutes. Further, 20 g of a 40% by
weight tetrabutylammonium hydroxide solution was added dropwise thereto
over 10 minutes. Then, stirring was continued at the same temperature and
solid was precipitated in about 15 minutes to form slurry. 200 g of
ion-exchanged water was added to slurry. The mixture was cooled to an
inner temperature of 25° C. and stirred and maintained at the same
temperature for 24 hours. Then, solid was collected by filtration. Solid
filtrated was washed twice with 100 g of ion-exchanged water, dried at
110° C. for 6 hours and calcined at 550° C. for 6 hours to
obtain 15.9 g of a white molybdenum-containing silicate.

[0115]XRD spectrum: A broad peak having an apex at a d value of 3.79 Å
is observed. A sharp peak assignable to tungsten oxide is not observed.

[0120]To a 500 mL flask equipped with a stirrer, 1.3 g of a vanadium metal
powder and 25 g of ion-exchanged water were added, and an inner
temperature was adjusted to 40° C. 15 g of a 30% by weight aqueous
hydrogen peroxide solution was added dropwise thereto over 30 minutes,
and then the mixture was maintained at the same temperature for 1 hour to
obtain a solution containing vanadium oxide. To the solution containing
vanadium oxide, 75 g of ion-exchanged water and 80 g of ethanol were
added, and then 41.6 g of tetraethoxysilane was added thereto at an inner
temperature of 40° C. over 10 minutes. Further, 40 g of a 40% by
weight tetra-n-propylamine solution was added dropwise thereto over 10
minutes. Then, the mixture was cooled to an inner temperature of
25° C. and stirring was continued and solid was precipitated in
about 30 minutes to form slurry. The slurry was stirred and maintained at
the same temperature for 24 hours. Then, solid was collected by
filtration. Solid filtrated was washed twice with 100 g of ion-exchanged
water, dried at 130° C. for 8 hours and calcined at 550° C.
for 6 hours to obtain 16.0 g of a brown vanadium-containing silicate.

[0121]XRD spectrum: A broad peak having an apex at a d value of 3.85 Å
is observed. A sharp peak assignable to vanadium oxide is not observed.

[0126]To a 50 mL flask equipped with a magnetic stirrer and a reflux
condenser, 30 mg of the molybdenum-containing silicate obtained in the
above-mentioned Reference Example 4, 310 mg of 1,2-epoxy-3-butene and 3 g
of distilled water were added. The resultant mixture was stirred at an
inner temperature of 25° C. for 5 hours to effect reaction. 10 g
of tetrahydrofuran was added to the reaction liquid obtained to obtain a
solution containing 3-butene-1,2-diol. The solution was analyzedby gas
chromatography internal standard method to find the yield of
3-butene-1,2-diol was 93%.

Example 2

[0127]According to a similar manner as that of Example 1, the reaction was
conducted except that the vanadium-containing silicate obtained in the
above-mentioned Reference Example 5 was used in place of the
molybdenum-containing silicate obtained in the above-mentioned Reference
Example 4 and 300 mg of 1,2-epoxy-3-butene was used.

[0128]The yield of 3-butene-1,2-diol was 94%.

Example 3

[0129]According to a similar manner as that of Example 1, the reaction was
conducted except that the molybdenum-containing silicate obtained in the
above-mentioned Reference Example 3 was used in place of the
molybdenum-containing silicate obtained in the above-mentioned Reference
Example 4 and 330 mg of 1,2-epoxy-3-butene was used.

[0130]The yield of 3-butene-1,2-diol was 95%.

Example 4

[0131]According to a similar manner as that of Example 1, the reaction was
conducted except that the tungsten-containing silicate obtained in the
above-mentioned Reference Example 1 was used in place of the
molybdenum-containing silicate obtained in the above-mentioned Reference
Example 4.

[0132]The yield of 3-butene-1,2-diol was 81%.

Example 5

[0133]According to a similar manner as that of Example 1, the reaction was
conducted except that the tungsten-containing silicate obtained in the
above-mentioned Reference Example 2 was used in place of the
molybdenum-containing silicate obtained in the above-mentioned Reference
Example 4.

[0134]The yield of 3-butene-1,2-diol was 82%.

Example 6

[0135]Into a 50 mL flask equipped with a magnetic stirrer and a reflux
condenser, 30 mg of the vanadium-containing silicate obtained in the
above-mentioned Reference Example 5, 300 mg of 1,2-epoxy-3-butene and 3 g
of distilled water were charged. The resultant mixture was stirred at an
inner temperature of 25° C. for 5 hours to effect reaction. 10 g
of tetrahydrofuran was added to the reaction liquid obtained, and then
the vanadium-containing silicate was separated by decantation to obtain a
solution containing 3-butene-1,2-diol. The solution was analyzed by gas
chromatography internal standard method to find the yield of
3-butene-1,2-diol was 94%.

Example 7

[0136]Into a 50 mL flask equipped with a magnetic stirrer and a reflux
condenser, all amount of the vanadium-containing silicate separated by
decantation in the above-mentioned Example 6, 300 mg of
1,2-epoxy-3-butene and 3 g of distilled water were charged. The resultant
mixture was stirred at an inner temperature of 25° C. for 5 hours
to effect reaction. 10 g of tetrahydrofuran was added to the reaction
liquid obtained to obtain a solution containing 3-butene-1,2-diol. The
solution was analyzed by gas chromatography internal standard method to
find the yield of 3-butene-1,2-diol was 87%.

Example 8

[0137]Into a 50 mL flask equipped with a magnetic stirrer and a reflux
condenser, 30 mg of 85% phosphoric acid, 300 mg of 1,2-epoxy-3-butene and
3 g of distilled water were charged. The resultant mixture was stirred at
an inner temperature of 5° C. for 5 hours to effect reaction. 10 g
of tetrahydrofuran was added to the reaction liquid obtained to obtain a
solution containing 3-butene-1,2-diol. The solution was analyzed by gas
chromatography internal standard method to find the yield of
3-butene-1,2-diol was 92%.

Example 9

[0138]Into a 50 mL flask equipped with a magnetic stirrer and a reflux
condenser, 30 mg of metaphosphoric acid, 300 mg of 1,2-epoxy-3-butene and
3 g of distilled water were charged. The resultant mixture was stirred at
an inner temperature of 5° C. for 5 hours to effect reaction. 10 g
of tetrahydrofuran was added to the reaction liquid obtained to obtain a
solution containing 3-butene-1,2-diol. The solution was analyzed by gas
chromatography internal standard method to find the yield of
3-butene-1,2-diol was 86%.

Example 10

[0139]To a 100 ml flask equipped with a magnetic stirrer, 880 mg of
3-butene-1,2-diol and 10 mg of 2,2'-azobisisobutyronitrile were added.
Into the mixture obtained, gaseous methanethiol was blowed at an inner
temperature of 25° C. with stirring at a speed of about 10 to 20
mL/min. over 1 hour. The mixture was further stirred at the same
temperature for 1 hour to effect reaction. After completion of the
reaction, methanethiol remained was removed by blowing nitrogen into the
reaction mixture, and 1245 mg of the oily matter containing
4-(methylthio)butane-1,2-diol was obtained. This oily matter was analyzed
by gas chromatography area percentage method to find the yield of
4-(methylthio)butane-1,2-diol was 73%.

Example 11

[0140]To a 100 ml autoclave equipped with a magnetic stirrer, 1300 mg of
3-butene-1,2-diol and 20 mg of 2,2'-azobisisobutyronitrile were added.
After cooling the mixture obtained at an inner temperature of 0°
C., 1400 mg of liquid methanethiol was added thereto. The autoclave was
sealed, and then the mixture was stirred at 30° C. for 2 hours to
effect reaction. The pressure (gauge pressure) of internal autoclave at
the point of starting the reaction was 2 kg/cm2 (equivalent of 0.2
MPa) and the pressure (gauge pressure) of internal autoclave at the point
of completion of the reaction was 1 kg/cm2 (equivalent of 0.1 MPa).
After completion of the reaction, methanethiol remained was removed by
blowing nitrogen into the reaction mixture, and 1790 mg of the oily
matter containing 4-(methylthio)butane-1,2-diol was obtained. This oily
matter was analyzed by gas chromatography area percentage method to find
the yield of 4-(methylthio)butane-1,2-diol was 67%.

Example 12

[0141]To a 100 ml autoclave equipped with a magnetic stirrer, 1300 mg of
3-butene-1,2-diol and 20 mg of azobisisobutyronitrile were added. After
cooling the mixture obtained at an inner temperature of 0° C.,
1400 mg of liquid methanethiol was added thereto. The autoclave was
sealed, and then the mixture was stirred at 40° C. for 4 hours to
effect reaction. The pressure (gauge pressure) of internal autoclave at
the point of starting the reaction was 2.5 kg/cm2 (equivalent of
0.25 MPa) and the pressure (gauge pressure) of internal autoclave at the
point of completion of the reaction was 0.5 kg/cm2 (equivalent of
0.05 MPa). After completion of the reaction, methanethiol remained was
removed by blowing nitrogen into the reaction mixture, and 1990 mg of the
oily matter containing 4-(methylthio)butane-1,2-diol was obtained. This
oily matter was analyzed by gas chromatography area percentage method to
find the yield of 4-(methylthio)butane-1,2-diol was 94%.

Example 13

[0142]To a 50 ml autoclave equipped with a magnetic stirrer, 2000 mg of
3-butene-1,2-diol and 20 mg of 2,2'-azobis[2-(2-imidazolin-2-yl)propane]
were added. After cooling the mixture obtained at an inner temperature of
0° C., 1500 mg of liquid methanethiol was added thereto. The
autoclave was sealed, and then the mixture was stirred at 40° C.
for 4 hours to effect reaction. The pressure (gauge pressure) of internal
autoclave at the point of starting the reaction was 2.5 kg/cm2
(equivalent of 0.25 MPa) and the pressure (gauge pressure) of internal
autoclave at the point of completion of the reaction was 0.5 kg/cm2
(equivalent of 0.05 MPa). After completion of the reaction, methanethiol
remained was removed by blowing nitrogen into the reaction mixture, and
10 g of ethyl acetate was added thereto to obtain the solution containing
4-(methylthio)butane-1,2-diol. The solution obtained was analyzed by gas
chromatography internal standard method to find the yield of
4-(methylthio)butane-1,2-diol was 94%.

Example 14

[0143]According to a similar manner as that of Example 13, the solution
containing 4-(methylthio)butane-1,2-diol was obtained except that methyl
azobisisobutyrate was used in place of
2,2'-azobis[2-(2-imidazolin-2-yl)propane]. The solution obtained was
analyzed by gas chromatography internal standard method to find the yield
of 4-(methylthio)butane-1,2-diol was 98%.

Example 15

[0144]To a 50 ml autoclave equipped with a magnetic stirrer, 2000 mg of
3-butene-1,2-diol, 9 mg of pyridine and 14 mg of acetic acid were added.
After cooling the mixture obtained at an inner temperature of 0°
C., 1500 mg of liquid methanethiol was added thereto. The autoclave was
sealed, and then the mixture was stirred at 40° C. for 4 hours to
effect reaction. The pressure (gauge pressure) of internal autoclave at
the point of starting the reaction was 2.5 kg/cm2 (equivalent of
0.25 MPa) and the pressure (gauge pressure) of internal autoclave at the
point of completion of the reaction was 0.5 kg/cm2 (equivalent of
0.05 MPa). After completion of the reaction, the pressure was released to
the ordinary pressure and methanethiol remained was removed by blowing
nitrogen into the reaction mixture, and 10 g of ethyl acetate was added
thereto. This solution was analyzed by gas chromatography internal
standard method to find the yield of 4-(methylthio)butane-1,2-diol was
94%.

Example 16

[0145]The predetermined amount of water was added to the colorless oil
obtained in Example 10 and insoluble matters was filtered off to prepare
a 10% (w/v) aqueous 4-(methylthio)butane-1,2-diol solution.

[0146]5 ML of culturing medium after sterilization (those obtained by
adding 20 g of glucose, 5 g of polypeptone, 3 g of yeast extract, 3 g of
meat extract, 0.2 g of ammonium sulfate, 1 g of potassium
dihydrogensulfate and 0.5 g of magnesium sulfate heptahydride thereto and
adjusting pH thereof to 7.0) was added to the test tube, and various
cells showed in Tables 1 to 4 were inoculated thereto. The shaking
culture was conducted under an aerobic condition at 30° C. After
completion of the culturing, the cells were separated by centrifugal
separation to obtain a viable fungus. To the screw cap test tube, 2 mL of
0.1 M potassium phosphate buffer (pH 7) was added and the above-mentioned
viable fungus was added thereto. 0.2 mL of the above-mentioned 10% (w/v)
aqueous 4-(methylthio)butane-1,2-diol solution was added thereto and
then, the mixture obtained was shaken at 30° C. for 2 to 3 days.
After completion of the reaction, 1 mL of the reaction liquid was
sampled. The cells were removed from the sampled liquid and the amount of
2-hydroxy-4-methylthiobutyric acid generated was analyzed by the liquid
chromatography. The results obtained are shown in Tables 1 to 4. The
formation rate (%) of 2-hydroxy-4-(methylthio)butyric acid was calculated
based on 4-(methylthio)butane-1,2-diol.

[0147]The analytical condition of the liquid chromatography is followed.